138 PROCEEDINGS OF SECTION B. — SUB-SECTION, PHARMACY. 



that an investigation of physiologically active substances produced by 

 the putrefaction of proteins might furnish a clue to the nature of the 

 other active ergot constituents, and suggest methods for their isolation. 

 A resemblance between ergot constituents and the products of putre- 

 faction was, indeed, suggested by Buchheim as long ago as 1874. But 

 the significance of this suggestion, as of Tanret's work on the alkaloids, 

 which followed a year later, had been obscured by the investigations 

 of the intermediate period. Barger and Walpole accordingly studied 

 the pressor constituents which occur in putrid muscle extracts, as 

 Abelous and his pupils had previously shown. They found them to 

 belong to the series of amines, formed from amino-acids by sphtting 

 off carbon dioxide, the most abundant being isoamylamine (from 

 leucine), the most active p-hydroxyphenylethylamine (from tyrosine). 

 Dale and Dixon showed that the action of these bas^ is of the same 

 general type as that of the supra-renal active principle. Meanwhile, 

 the probability that the other active constituents of ergot were to be 

 sought in this direction was increased by the work of Rielander, who 

 extracted from ergot the well-known but almost inactive bases putres- 

 cine and cadaverine. Applying the experience gained with putrid 

 meat, Barger was able to prove the presence of the pressor amines in the 

 ordinary liquid extract of ergot, and to show, in conjunction with Dale, 

 that practically the whole of the adrenine-like pressor action possessed 

 by such extracts, and widely used in England at the time as a basis for 

 their physiological standardization, was due to the presence of 

 p-hydroxyphenylethylamine. This substance has been produced 

 artificially by a number of synthetic methods, and is now obtainable 

 commercially under the name " tyramine." 



The investigation was not yet complete, for " tyramine " was 

 found to resemble adrenine, not merely in its pressor action, but in 

 practically all its effects, reproducing very closely the effects of 

 stimulating nerves of the true sympathetic system. Among such, a 

 highly characteristic action is the inhibition of the tone and rhythm of 

 the uterus of the virgin cat, and this is typically reproduced by 

 "tyramine." On the other hand, it has been shown by Kehrer that 

 isolated uterine muscle from any animal responds by tonic contraction to 

 small doses of ergot extracts, and that the uterus of the non-pregnant 

 cat exhibits this effect particularly well. Though ergotoxine has a 

 powerful tonic effect on the cat's uterus in situ, it has a comparatively 

 weak action on the isolated organ ; it was clear, therefore, that some 

 other principle must be present of sufficient power in this direction to 

 overcome the inhibitor effect of tyramine. In searching for this, Barger 

 and Dale made use of the methods elaborated by Kutscher and his 

 school for the separation of bases from extracts of meat or putrefaction 

 mixtures. 



